title: Pharmacokinetics of flunixin in mature heifers following multiple intravenous administration.
abstract: The pharmacokinetics of flunixin meglumine was determined after its multiple (altogether 4 doses at 24-hours intervals) intravenous administration at a dose of 2.2 mg/kg body weight in six mature clinically healthy heifers. Plasma flunixin and its metabolite 5-hydroxyflunixin concentrations were analyzed with high-pressure liquid chromatography using an assay with a lower limit detection of 0.03 microg/ml for both substances. Plasma concentrations versus time curves were described by a two compartment open model. Mean plasma flunixin concentrations were similar on day 1 and 4, and than rapidly decreased (within 2 hours) from initial concentrations higher than 10 microg/ml to the concentrations lower than 1 microg/ml. The distribution phase of flunixin was short (t0.5 alpha = 0.29 +/- 0.16 and 0.18 +/- 0.04 on day 1 and 4, respectively) and the elimination phase was more prolonged (t0.5 beta = 3.30 +/- 0.60 and 3.26 +/- 0.22 on day 1 and 4, respectively). The mean residence time of flunixin was similar on day 1 (1.83 +/- 0.83) and 4 (1.88 +/- 0.46), and for 5-hydroxyflunixin this parameter was insignificantly (P > 0.05) higher on day 1 (5.49 +/- 2.22) as compared to that found on day 4 (3.99 +/- 2.17). The clearance of flunixin was similar on both examined days (0.23 +/- 0.12 on day 1 and 0.31 +/- 0.15 on day 4), and for 5-hydroxyflunixin was insignificantly (P > 0.05) lower on day 1 (2.37 +/- 1.21) as compared to that determined on day 4 (3.23 +/- 1.06). Our data indicate that multiple administration of flunixin did not alter significantly the parent drug and its metabolite concentrations in plasma, however may cause some small changes in pharmacokinetic parameters.
authors.affiliation: Division of Pharmacology, Department of Pathology and Pharmacology, Faculty of Veterinary Medicine, University of Warmia and Mazury, 10-719 Olsztyn, Poland. jerzyj@uwm.edu.pl
authors.forename: J
authors.initials: J
authors.lastname: Jaroszewski
authors.forename: P
authors.initials: P
authors.lastname: Jedziniak
authors.forename: W
authors.initials: W
authors.lastname: Markiewicz
authors.forename: T
authors.initials: T
authors.lastname: Grabowski
authors.forename: M
authors.initials: M
authors.lastname: Chrostowska
authors.forename: T
authors.initials: T
authors.lastname: Szprengier-Juszkiewicz
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002417:Cattle / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000662:veterinary; D003002:Clonixin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D008657:Metabolic Clearance Rate; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C014558:flunixin meglumine; D003002:Clonixin